We have successfully replaced all of the blood of living rats with protein-free artificial preparations. These animals have survived, rapidly regenerated both blood cells and proteins, and continued to grow normally. The objectives of the proposed research are (a) to continue the development of these artificial preparations for use in the whole blood replacement in vivo and in vitro, and (b) to explore further the physiological, biochemical, and nutritional aspects of animals and isolated organs sustained by these preparations. Because of the complexity of whole blood, no simple synthetic mixture is capable of providing all of the properties and functions of normal blood. Therefore, the approach used in these studies will be to satisfy the osmotic pressure, oncotic pressure, and gas transport requirements, while avoiding insofar as possible adverse effects on the animals' blood and vascular system during and after the exchange transfusion. Liquid fluorocarbons will be used for oxygen and carbon dioxide transport, high molecular weight polyols for dispersing the fluorocarbons and for furnishing oncotic pressure, and electrolytes and glucose for osmotic pressure. The fluorocarbon-polyol system is versatile, allowing the preparation of both emulsions having 0.3 to 1 micron particles, and water-clear type products. These various preparations differ widely in their properties and will be compared for effectiveness in both living animals and isolated tissues.. Physiological and biochemical measurements will be made, and the fate of the fluorocarbons used in vivo and in vitro and of the polyols will be investigated. Organs perfused with the preparations will be studied from the standpoints of preservation, metabolism, and nutrition.